This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With the advent of nano-needles, and their use in nanomedicine, scientists are able to inject small quantities of pharmaceuticals into a single cell. It is theorized that the small dimensions of the needle minimize membrane disruption and do not compromise the viability of the cells themselves. However, we require a fundamental understanding of the mechanisms activated during injection, and the magnitude of cell disruption due to needle size and chemistry of both the needle and the membrane. The carbon nanotube is an excellent choice for molecular needle due to its mechanical integrity and long aspect ratio. We propose to expand on our studies of cell membrane penetration using Molecular Dynamics. Due to computational limitations, our previous studies focused on a penetration rate that was faster than some of the underlying dynamical processes. From these simulations, we were able to determine force-displacement curves, free energies of interaction, and study the molecular motion in the membrane induced by penetration. By varying the rate of indentation, we hope to probe the rate dependence of both the forces and mechanisms involved in this process. In addition, effects of membrane chemistry will be probed. At first, this will involve the penetration of cholesterol containing membranes and later this can be expanded to study penetration of membranes of varying composition and structure.